One of the major problems facing our society today is the widespread use of addicting drugs by a great many individuals. Among the drug abuse problems in the United States, alcoholism is the most serious in terms of economic loss, loss in productivity and psychological damage to individuals and families. An estimated ten million people in this country are afflicted with serious drinking problems.
Second in importance is the dependence of an ever increasing segment of our population upon narcotic drugs, particularly among the younger people. In 1970 J. Ingersoll suggested that there are from 120,000 to 180,000 heroin users in this country alone, i.e., a ratio of 1 in 1,100 to 1 in 1,700 persons (Statement before the U.N. Commission on Narcotic Drugs, Sept. 28, 1970).
Again, the habit forming tendencies of tobacco are well known, as are the symptoms of tobacco withdrawal. Moreover, it is now well documented that tobacco consumption, paritcularly in the form of cigarette smoking, is hazardous to one's health. Smoking has been implicated as a causative agent in such conditions as emphysema, lung, mouth and throat cancer, the aggravation of hypertension, atherosclerosis and in coronary artery disease. Of the millions of people in this country who voluntarily attempt to give up smoking each year, the long term success rate at present is only 3%.
There appears to be no common denominator for the dependency of these various drug substances. Drug dependency occurs in people of all ages, having diverse backgrounds and at every socio-economic level. The one generalization that can be made, however, is that following a period of drug dependency, most individuals seek to escape their drug dependency but find it extremely difficult to do. This is true whether the dependency is one based on narcotic substances, other drugs, tobacco or alcohol. In the case of narcotics substances, and in particular opiates, withdrawal is virtually impossible absent conrtrolled and carefully monitored hospital treatment. Moreover, the severe withdrawal symptoms that are endured, frequently have a deleterious effect upon the physical, mental and emotional well-being of the individual. In the case of alcoholism, multiple detoxifications during the course of an individual's lifetime are the rule.
Inasmuch as opiates and other drugs have certain behavioral and biochemical effects which appear to involve catecholamine neurotransmitter systems, investigators have tried to mimic the withdrawal of these drugs by administering drugs which antagonize these transmitter systems. U.S. Pat. No. 3,923,987 illustrates one such attempt using pharmaceutical compositions consisting of N-(furyl or thienylmethyl)-14-oxy-7,8-dihydronormorphinone or norcodeinone in an effort to antagonize the effects of opiate dependency. Deoxycytidine, a morphine antagonist, is also stated to be useful for the treatment of morphine addiction and toxification, see U.S. Pat. No. 3,873,698.
These approaches have not met with much success, however, and the usual treatment for narcotic or opiate withdrawal involves maintenance therapy. Maintenance therapy is a relatively new approach to narcotic addiction, pioneered predominately by Dole and Co-workers (Arch. Int. Med. 118, 304 (1966); J. Am. Med. Assn., 206, 2708 (1968) and New. Engl. J. Med. 280, 1372 (1969), wherein a narcotic substitute is administered in lieu of the drug substance. The narcotic substitute most frequently used in maintenance therapy is methadone, more particularly the hydrochloride salt of methadone.
Detoxification via methadone maintenance, however, is a slow and difficult process with patients frequently experiencing abstinence and withdrawal symptoms due to methadone itself. Moreover, methadone maintenance is potentially subject to abuse when administered intravenously so as to obtain potentiated narcotic effects.
Recent studies have shown that clonidine, 2-(2,6-dichloroanilino)-2-imidazoline relieves certain symptoms of opiate withdrawal, Washton et al., Lancet, pp. 1078-9 (1980) and Gold et al., J. Am. Med. Assn. 243, pp. 343-6 (1980). Additionally, clonidine has been suggested as a useful aid in the treatment of alcohol withdrawal, Bjorkqvist, Acta Psychiat. Scand. 52, pp. 256-63 (1975). However, due to oversedation and the potentially serious decrease in blood pressure in some patients, this method of detoxification requires the close supervision of an inpatient setting. Moreover, many patients develop a tolerance to the sedative effect of clonidine after several days and require additional night time sedation to alleviate insomnia.
Thus, it can be seen that there exists an urgent need for a drug that is useful in alleviating the effects of withdrawal from a wide variety of addicting drug substances, which drug is safe and non-addicting in and of itself, and which does not possess the serious disadvantages of some of the compounds used in the past for this purpose.